The facile synthesis and photophysical properties of three non-hydrolysable thioglycosylated porphyrinoids are reported. Starting from meso perfluorophenylporphyrin, the non-hydrolysable thioglycosylated porphyrin (PGlc4), chlorin (CGlc4), isobacteriochlorin (IGlc4), and bacteriochlorin (BGlc4) can be made in 2–3 steps. The ability to append a wide range of targeting agents onto the perfluorophenyl moieties, the chemical stability, and the ability to fine-tune the photophysical properties of the chromophores make this a suitable platform for development of biochemical tags, diagnostics, or as photodynamic therapeutic agents. Compared to the porphyrin in phosphate buffered saline, CGlc4 has a markedly greater absorbance of red light near 650 nm and a 6-fold increase in fluorescence quantum yield; whereas IGlc4 has broad Q bands and a 12-fold increase in fluorescence quantum yield. BGlc4 has a similar fluorescence quantum yield to PGlc4, (<10%) but the lowest energy absorption/emission peaks of BGlc4 are considerably red shifted to near 730 nm with a nearly 50-fold greater absorbance, which may allow this conjugate to be an effective PDT agent. The uptake of CGlc4, IGlc4, and BGlc4 derivatives into cells such as human breast cancer cells MDA-MB-231 and K:Molv NIH 3T3 mouse fibroblast cells can be observed at nM concentrations. Photobleaching under these conditions is minimal.

The four para fluoro groups on 5,10,15,3,4,5, ) are known to react with a variety of nucleophiles, but the reaction conditions for this substitution reaction depend on the nature of the nucleophiles, e.g. primary amines versus thiols. Glycosylated derivatives of this core porphyrin have been shown to be effective photodynamic agents in the induction of necrosis or apoptosis in several cancer cell lines. The present report demonstrates that TPPF 20 can be used as a core platform to efficiently generate a variety of solution phase combinatorial libraries. The focused combinatorial libraries have substituents that are chosen from a set of motifs known to bind biopolymers such as DNA, be taken up by cancer cells, or to render the compounds amphipathic. Incubation of a breast cancer cell line with these solution phase libraries, followed by cell lyses and extraction, affords a selection assay. MALDI mass spectrometry of the extracts allows identification of the molecules taken up by the cells. Cell binding assays of the winning compounds synthesized directly, indicate that both glycosylation and amphipathicity are key properties since neither tetraglycosylated porphyrins nor those with four polar groups are selected to the same extent. In addition, photodynamic efficacy was evaluated.